Glycosylation of Anthocyanins Enhances the Apoptosis of Colon Cancer Cells by Handicapping Energy Metabolism

Overview

Journal BMC Complement Med Ther

Publisher Biomed Central

Specialty Rehabilitation Medicine

Date 2020 Oct 16

PMID 33059637

Citations 9

Authors

Nan Jing

Jiaxing Song

Zheng Liu

Luoyang Wang

Guoqiang Jiang

Affiliations

Soon will be listed here.

Abstract

Background: While anthocyanins are proven to be effective in inhibiting tumour cell proliferation, the underlying mechanisms remain unclear. This research aims to explore the glycosylation of anthocyanins in the tumour inhibitory effects and the potential mechanism.

Methods: The tumour inhibitory effect on mouse colon cancer cells (MC38) was examined by MTT and flow cytometric analyses. The inhibitory pathway of anthocyanin was explored by assessment of tumour cell mitochondrial membrane potential (MMP), the caspase-3 and caspase-9 activity, as well as the cell energy metabolism in terms of the glucose uptake, the NAD/NADH ratio and the ATP level.

Results: We found that 500 μM bilberry anthocyanins extract (BAE) induced 48.1% mitochondrial damage, activated the downstream caspase cascade to form apoptotic bodies (caspase-3 activity increased by 169%, caspase-9 activity increased by 186%), and inhibited cell proliferation (survival rate: 55.97%, 24 h). In contrast, the same concentration of anthocyanidin (cyanidin) led to marginal mitochondrial damage (only 9.85%) and resulted in little inhibition of MC38 cells (survival rate: 86.84%, 24 h). For cells incubated with 500 μM BAE, reactive oxygen species (ROS) decreased by 53.8%, but the ratio of NAD/NADH increased to 3.67, demonstrating that the mitochondrial damage was induced by blocking energy metabolism. Furthermore, cell energy metabolism is related to glucose uptake since the presence of 200 μM GLUT1 inhibitor substantially enhanced the inhibitory effects of cyanidin-3-O-glucoside (Cy-3-Glu) at 500 μM (survival rate: 51.08%, 24 h).

Conclusions: The study suggested that the glycosides of anthocyanins might handicap glucose transport and inhibit energy metabolism, which, in turn, led to mitochondrial damage and apoptosis of tumour cells.

Citing Articles

Oral intake of Hibiscus sabdariffa L. increased c-Myc and caspase-3 gene expression and altered microbial population in colon of BALB/c mice induced to preneoplastic lesions.

Ladeira Bernardes A, Albuquerque Pereira M, Xisto Campos I, Avila L, Dos Santos Cruz B, Duarte Villas Mishima M Eur J Nutr. 2025; 64(3):109.

PMID: 40042671 DOI: 10.1007/s00394-025-03622-z.

From Waste to Value: Optimization of Ultrasound-Assisted Extraction of Anthocyanins and Flavonols from L. Oilcakes.

Muti L, Dos Santos Nascimento L, Goracci G, Detti C, Brunetti C, Bilia A Molecules. 2025; 30(2).

PMID: 39860107 PMC: 11767306. DOI: 10.3390/molecules30020237.

Health-Promoting Properties of Anthocyanins from Cornelian Cherry ( L.) Fruits.

Szot I, Lysiak G, Sosnowska B, Chojdak-Lukasiewicz J Molecules. 2024; 29(2).

PMID: 38257363 PMC: 10818799. DOI: 10.3390/molecules29020449.

Berries vs. Disease: Revenge of the Phytochemicals.

Lamenza F, Upadhaya P, Roth P, Shrestha S, Jagadeesha S, Horn N Pharmaceuticals (Basel). 2024; 17(1).

PMID: 38256917 PMC: 10818490. DOI: 10.3390/ph17010084.

The Role of Cyanidin-3--glucoside in Modulating Oxaliplatin Resistance by Reversing Mesenchymal Phenotype in Colorectal Cancer.

Kurter H, Basbinar Y, Ellidokuz H, Calibasi-Kocal G Nutrients. 2023; 15(22).

PMID: 38004099 PMC: 10674439. DOI: 10.3390/nu15224705.

References

Hidalgo J, Teuber S, Morera F, Ojeda C, Flores C, Hidalgo M . Delphinidin Reduces Glucose Uptake in Mice Jejunal Tissue and Human Intestinal Cells Lines through FFA1/GPR40. Int J Mol Sci. 2017; 18(4). PMC: 5412335. DOI: 10.3390/ijms18040750. View

Li M, Song M, Ren L, Xiu C, Liu J, Zhu Y . AlCl3 induces lymphocyte apoptosis in rats through the mitochondria-caspase dependent pathway. Environ Toxicol. 2014; 31(4):385-94. DOI: 10.1002/tox.22051. View

Chen W, Feng L, Shen Y, Su H, Li Y, Zhuang J . Myricitrin inhibits acrylamide-mediated cytotoxicity in human Caco-2 cells by preventing oxidative stress. Biomed Res Int. 2013; 2013:724183. PMC: 3809942. DOI: 10.1155/2013/724183. View

Moskvin M, Babic M, Reis S, Cruz M, Ferreira L, Carvalho M . Biological evaluation of surface-modified magnetic nanoparticles as a platform for colon cancer cell theranostics. Colloids Surf B Biointerfaces. 2017; 161:35-41. DOI: 10.1016/j.colsurfb.2017.10.034. View

Gowd V, Bao T, Wang L, Huang Y, Chen S, Zheng X . Antioxidant and antidiabetic activity of blackberry after gastrointestinal digestion and human gut microbiota fermentation. Food Chem. 2018; 269:618-627. DOI: 10.1016/j.foodchem.2018.07.020. View

Porter A, Janicke R . Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999; 6(2):99-104. DOI: 10.1038/sj.cdd.4400476. View

Cooke D, Steward W, Gescher A, Marczylo T . Anthocyans from fruits and vegetables--does bright colour signal cancer chemopreventive activity?. Eur J Cancer. 2005; 41(13):1931-40. DOI: 10.1016/j.ejca.2005.06.009. View

Zhang F, Shi J, Thakur K, Hu F, Zhang J, Wei Z . Anti-Cancerous Potential of Polysaccharide Fractions Extracted from Peony Seed Dreg on Various Human Cancer Cell Lines Via Cell Cycle Arrest and Apoptosis. Front Pharmacol. 2017; 8:102. PMC: 5334287. DOI: 10.3389/fphar.2017.00102. View

Long H, Zhang F, Wang H, Yang W, Hou H, Yu J . Mulberry anthocyanins improves thyroid cancer progression mainly by inducing apoptosis and autophagy cell death. Kaohsiung J Med Sci. 2018; 34(5):255-262. DOI: 10.1016/j.kjms.2017.11.004. View

10.

Cain K, Bratton S, Cohen G . The Apaf-1 apoptosome: a large caspase-activating complex. Biochimie. 2002; 84(2-3):203-14. DOI: 10.1016/s0300-9084(02)01376-7. View

11.

Alzaid F, Cheung H, Preedy V, Sharp P . Regulation of glucose transporter expression in human intestinal Caco-2 cells following exposure to an anthocyanin-rich berry extract. PLoS One. 2013; 8(11):e78932. PMC: 3827299. DOI: 10.1371/journal.pone.0078932. View

12.

Venancio V, Cipriano P, Kim H, Antunes L, Talcott S, Mertens-Talcott S . Cocoplum (Chrysobalanus icaco L.) anthocyanins exert anti-inflammatory activity in human colon cancer and non-malignant colon cells. Food Funct. 2016; 8(1):307-314. DOI: 10.1039/c6fo01498d. View

13.

Manzano S, Williamson G . Polyphenols and phenolic acids from strawberry and apple decrease glucose uptake and transport by human intestinal Caco-2 cells. Mol Nutr Food Res. 2010; 54(12):1773-80. DOI: 10.1002/mnfr.201000019. View

14.

Wang Y, Fang F, Wong C . Troglitazone is an estrogen-related receptor alpha and gamma inverse agonist. Biochem Pharmacol. 2010; 80(1):80-5. DOI: 10.1016/j.bcp.2010.03.013. View

15.

Li J, Wu T, Li N, Wang X, Chen G, Lyu X . Bilberry anthocyanin extract promotes intestinal barrier function and inhibits digestive enzyme activity by regulating the gut microbiota in aging rats. Food Funct. 2018; 10(1):333-343. DOI: 10.1039/c8fo01962b. View

16.

Kapoor S . Glucose transporter 1 (GLUT1) and its emerging role as a significant prognostic marker in systemic malignancies. Int J Colorectal Dis. 2012; 28(9):1317-8. DOI: 10.1007/s00384-012-1610-8. View

17.

Malik M, Zhao C, Schoene N, Guisti M, Moyer M, Magnuson B . Anthocyanin-rich extract from Aronia meloncarpa E induces a cell cycle block in colon cancer but not normal colonic cells. Nutr Cancer. 2003; 46(2):186-96. DOI: 10.1207/S15327914NC4602_12. View

18.

Seeram N . Berry fruits: compositional elements, biochemical activities, and the impact of their intake on human health, performance, and disease. J Agric Food Chem. 2008; 56(3):627-9. DOI: 10.1021/jf071988k. View

19.

Hosseini F, Karimabad M, Hajizadeh M, Khoshdel A, Khanamani Falahati-Pour S, Mirzaei M . Evaluating of Induction of Apoptosis by Cornus mass L. Extract in the Gastric Carcinoma Cell Line (AGS). Asian Pac J Cancer Prev. 2019; 20(1):123-130. PMC: 6485578. DOI: 10.31557/APJCP.2019.20.1.123. View

20.

Hu D, Xu Y, Xie J, Sun C, Zheng X, Chen W . Systematic evaluation of phenolic compounds and protective capacity of a new mulberry cultivar J33 against palmitic acid-induced lipotoxicity using a simulated digestion method. Food Chem. 2018; 258:43-50. DOI: 10.1016/j.foodchem.2018.03.049. View